Previous investigations have shown that acetaldehyde, the primary metabolite of ethanol, reacts with tissue homogenates containing epinephrine (3a) and norepinephrine (3b) or with these catecholamines alone to produce products previously thought to be tetrahydroisoquinolines 4a and 4b respectively. The crude epinephrine-acetaldehyde condensate possesses profound physiological activity, suggesting that it may indeed be responsible for some of the effects of ethanol including intoxication, dependence, withdrawal, and neural degeneration. In the proposed research, we plan to structurally define the chemical nature of these biologically active molecules. A preliminary investigation in this laboratory revealed that the epinephrine-acetaldehyde reaction produces a mixture of compounds in which cis and trans which 4a are only minor constituents. Our first goal is the separation isolation and complete structural characterization of the components which our preliminary studies suggest may include isomeric tetrahydroisoquinolines 5a. Subsequently we propose to synthesize sufficient quantities of these compounds for biological testing to enable an evaluation of what role they play in mediating the effects of ethanol. Clear definition of this role should ultimately lead to better prospects for intervention and treatment of alcoholism.